Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Fritz Pregl Strasse 3, 6020 Innsbruck, Austria.
Inflamm Res. 2011 Feb;60(2):127-35. doi: 10.1007/s00011-010-0244-y. Epub 2010 Aug 26.
Inflammation is crucially involved in a variety of diseases like autoimmune syndromes, cardiovascular and neurodegenerative disorders, cancer, sepsis and allograft rejection.
Freshly isolated human peripheral blood mononuclear cells (PBMCs) are used as a screening assay for anti-inflammatory properties of compounds. Determinations of neopterin production by ELISA and of tryptophan degradation by HPLC are used as read-outs. Results are compared with further markers of immune response and oxidative stress.
Phytohaemagglutinin induced significant tryptophan degradation and neopterin formation in PBMC, which correlated with IFN-γ, TNF-α, soluble cytokine receptors and isoprostane-8. Addition of vitamin C and E suppressed the responses dose-dependently.
The determination of tryptophan degradation and neopterin production in PBMC reflects various pro- and anti-inflammatory cascades that are of relevance also in patients. It constitutes a robust and reliable approach to screen anti-inflammatory or immunosuppressive drugs and may improve throughput, speed and cost-effectiveness in drug discovery.
炎症在多种疾病中起着关键作用，如自身免疫综合征、心血管和神经退行性疾病、癌症、败血症和同种异体移植排斥。
新鲜分离的人外周血单核细胞 (PBMC) 被用作化合物抗炎特性的筛选检测。通过 ELISA 测定新蝶呤的产生和 HPLC 测定色氨酸的降解作为读出。结果与免疫反应和氧化应激的进一步标志物进行比较。
植物血球凝集素诱导 PBMC 中显著的色氨酸降解和新蝶呤形成，这与 IFN-γ、TNF-α、可溶性细胞因子受体和异前列烷-8 相关。维生素 C 和 E 的添加以剂量依赖性方式抑制反应。
PBMC 中色氨酸降解和新蝶呤产生的测定反映了各种促炎和抗炎级联反应，这些反应在患者中也很重要。它构成了一种强大而可靠的筛选抗炎或免疫抑制药物的方法，并可能提高药物发现的通量、速度和成本效益。
